HLA B*5701 Status, Disease Progression, and Response to ART
HLA B*5701 Status, Disease Progression, and Response to ART
A total of 8246 patients in the UK CHIC study had ever received a HLA B*5701 test, of whom 426 (5.2%) were positive. There were 3258 patients ever tested who were ART-naive at study entry and who were included in the study of the effects of HLA B*5701 status and viral load on CD4 cell count; 165 (5.1%) of this group had tested positive for HLA B*5701. Characteristics of these patients are given in Table 1(i). Median (interquartile range, IQR) CD4 cell count at entry was 511 (365–663) cells/μl in HLA B*5701-positive individuals and 395 (282–540) cells/μl in HLA B*5701-negative (P <0.0001). Median (IQR) viral load at study entry was 4.1 (3.3–4.6) and 4.5 (3.9–5.0) log10 copies/ml in those positive and negative, respectively (P <0.0001). In linear regression, both HLA B*5701 status and viral load were independently associated with CD4 cell count at entry after adjustment for age, sex, and ethnicity, with a mean (95% confidence interval, CI) CD4 cell count increase of 42 (10–74) cells/μl in HLA B*5701-positive individuals over negative and an 80 (72–88) cells/μl decrease for every log10 copy increase in viral load (results not shown). However, a test for an interaction between HLA B*5701 status and viral load did not suggest strong evidence that viral load had a differential impact on CD4 cell count in those who were positive for the allele and those negative (P = 0.088). Further, in linear regression models of all off-ART CD4 and viral load pairs and models restricted to those of white ethnicity, there was no evidence of an interaction between viral load and HLA B*5701 status (P = 0.76 and P = 0.95, respectively).
There were 3476 tested individuals who commenced a nonabacavir cART regimen following a test for HLA B*5701, 3201 of whom had follow-up of at least one CD4 cell count and viral load measurement. A further 6364 individuals who had not been tested commenced a nonabacavir regimen after 2005. Characteristics of all 9565 patients upon starting a nonabacavir regimen are shown in Table 1(ii). In the subgroup of ART-naive patients, HLA B*5701-positive individuals were more likely to achieve an undetectable viral load than negative [adjusted hazard ratio (AHR) = 1.60, 95% CI (1.28–2.01) (Table 2)]. HLA B*5701-positive patients also showed a decreased likelihood of experiencing viral rebound compared with negatives, although this result did not reach statistical significance [AHR = 0.57, 95% CI (0.23–1.39)]. There was a small reduction in the risk of treatment switch that was not significant [AHR = 0.86, 95% CI (0.60–1.22)]. Those not tested had a similar risk of viral rebound and treatment switch to HLA B*5701 negatives, but a slightly increased likelihood of achieving an undetectable viral load (hazard ratio = 1.15, 95% CI 1.06–1.24). Including ART-experienced patients in the analysis of virological response yielded similar results (Table 2). An increased likelihood of viral suppression was still present in positive patients compared with negative [AHR = 1.29, 95% CI (1.15–1.54)], as was the decreased risk of viral rebound, which was now significant [AHR = 0.61, 95% CI (0.37–0.99)] due to the larger number of individuals included in the analysis.
Immunological response to cART did not differ according to HLA B*5701 status. Being HLA B*5701-positive increased 6-month CD4 cell count change by 16.7 cells/μl [95% CI (-11.5–45.0)] on average compared with the 6-month change in negative patients. Twelve-month CD4 cell count change was in fact lower by approximately 28 cells/μl [95% CI (-62.3–5.8)] in positive patients compared with negative. There was no difference in 6-month [β = -10.6, 95% CI (-20.0–1.2)] or 12-month [β = 1.2, 95% CI (-10.5–12.9)] CD4 cell count change between those negative and those not tested for the allele.
Results
A total of 8246 patients in the UK CHIC study had ever received a HLA B*5701 test, of whom 426 (5.2%) were positive. There were 3258 patients ever tested who were ART-naive at study entry and who were included in the study of the effects of HLA B*5701 status and viral load on CD4 cell count; 165 (5.1%) of this group had tested positive for HLA B*5701. Characteristics of these patients are given in Table 1(i). Median (interquartile range, IQR) CD4 cell count at entry was 511 (365–663) cells/μl in HLA B*5701-positive individuals and 395 (282–540) cells/μl in HLA B*5701-negative (P <0.0001). Median (IQR) viral load at study entry was 4.1 (3.3–4.6) and 4.5 (3.9–5.0) log10 copies/ml in those positive and negative, respectively (P <0.0001). In linear regression, both HLA B*5701 status and viral load were independently associated with CD4 cell count at entry after adjustment for age, sex, and ethnicity, with a mean (95% confidence interval, CI) CD4 cell count increase of 42 (10–74) cells/μl in HLA B*5701-positive individuals over negative and an 80 (72–88) cells/μl decrease for every log10 copy increase in viral load (results not shown). However, a test for an interaction between HLA B*5701 status and viral load did not suggest strong evidence that viral load had a differential impact on CD4 cell count in those who were positive for the allele and those negative (P = 0.088). Further, in linear regression models of all off-ART CD4 and viral load pairs and models restricted to those of white ethnicity, there was no evidence of an interaction between viral load and HLA B*5701 status (P = 0.76 and P = 0.95, respectively).
There were 3476 tested individuals who commenced a nonabacavir cART regimen following a test for HLA B*5701, 3201 of whom had follow-up of at least one CD4 cell count and viral load measurement. A further 6364 individuals who had not been tested commenced a nonabacavir regimen after 2005. Characteristics of all 9565 patients upon starting a nonabacavir regimen are shown in Table 1(ii). In the subgroup of ART-naive patients, HLA B*5701-positive individuals were more likely to achieve an undetectable viral load than negative [adjusted hazard ratio (AHR) = 1.60, 95% CI (1.28–2.01) (Table 2)]. HLA B*5701-positive patients also showed a decreased likelihood of experiencing viral rebound compared with negatives, although this result did not reach statistical significance [AHR = 0.57, 95% CI (0.23–1.39)]. There was a small reduction in the risk of treatment switch that was not significant [AHR = 0.86, 95% CI (0.60–1.22)]. Those not tested had a similar risk of viral rebound and treatment switch to HLA B*5701 negatives, but a slightly increased likelihood of achieving an undetectable viral load (hazard ratio = 1.15, 95% CI 1.06–1.24). Including ART-experienced patients in the analysis of virological response yielded similar results (Table 2). An increased likelihood of viral suppression was still present in positive patients compared with negative [AHR = 1.29, 95% CI (1.15–1.54)], as was the decreased risk of viral rebound, which was now significant [AHR = 0.61, 95% CI (0.37–0.99)] due to the larger number of individuals included in the analysis.
Immunological response to cART did not differ according to HLA B*5701 status. Being HLA B*5701-positive increased 6-month CD4 cell count change by 16.7 cells/μl [95% CI (-11.5–45.0)] on average compared with the 6-month change in negative patients. Twelve-month CD4 cell count change was in fact lower by approximately 28 cells/μl [95% CI (-62.3–5.8)] in positive patients compared with negative. There was no difference in 6-month [β = -10.6, 95% CI (-20.0–1.2)] or 12-month [β = 1.2, 95% CI (-10.5–12.9)] CD4 cell count change between those negative and those not tested for the allele.
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